Isorhamnetin protects porcine oocytes from zearalenone-induced reproductive toxicity through the PI3K/Akt signaling pathway

Background Zearalenone(ZEA)widely exists in moldy grains,which seriously destroys the fertility of females.Isorhamnetin,a natural flavonoid,has extensive of pharmacological activities.However,the beneficial effect and the underlying molecular mechanism of isorhamnetin involvement in ZEA-induced porcine oocyte damage have not been investigated.Methods Oocytes were treated with different concentrations of ZEA(3,5,8 and 10μmol/L)and isorhamnetin(5,10,20 and 30μmol/L)for 44 h at 39℃.ZEA(5μmol/L)and isorhamnetin(10μmol/L)were selected for subsequent studies.Polar body exclusion rate,apoptosis rate and apoptosis related proteins,ROS levels and SOD2 protein,mitochondrial membrane potential and distribution,endoplasmic reticulum distribution and proteins expression,and PI3K,Akt and p-Akt proteins expression of oocytes were detected.In addition,the effect of PI3K antagonist(LY294002)on oocyte nuclear maturation and apoptosis were used to determine the involvement of PI3K/Akt signaling pathway.Results Our findings showed that ZEA exposure damaged oocytes and isorhamnetin therapy restored the developmental capability of porcine oocytes.Isorhamnetin promoted polar body extrusion rate to rescue ZEA-induced meiotic arrest in porcine oocytes.Isorhamnetin alleviated ZEA-induced oxidative stress by stimulating SOD2 protein expression and inhibiting ROS production.Moreover,isorhamnetin enhanced normal mitochondrial distribution and mitochondrial membrane potential to prevent mitochondrial dysfunction induced by ZEA.Changing the expression of endoplasmic reticulum stress-related marker proteins(CHOP,GRP78)and the distribution rate of normal endoplasmic reticulum showed that isorhamnetin relieved ZEA-caused endoplasmic reticulum stress.Mechanistically,isorhamnetin decreased Bax/Bcl-2 protein expression and inhibited ZEA-induced apoptosis through PI3K/Akt signaling pathway.Conclusions Collectively,these results suggest that isorhamnetin protects oocytes from ZEA-caused damage through PI3K/Akt signaling pathway,which enhances meiotic maturation and mitochondrial function,and inhibits early apoptosis,oxidative stress and endoplasmic reticulum stress in porcine oocytes.Our study provides a new strategy for solving the reproductive toxicity induced by ZEA and treating woman infertility.

Evaluation of the Relative Tectonic Activity from the Faults in the Gengma-Lancang-Menghai Seismic Belt(Southwestern China)

The Gengma-Lancang-Menghai seismic belt,the southernmost part of the North-South seismic belt,is controlled by four active faults:the Nantinghe fault(NTHF),the Sanjianshan fault(SJSF),the Hanmuba-Lancang fault(HMB-LCF),and the Heihe fault(HHF),from northwest to southeast.However,the tectonic activity of the faults in the Gengma-Lancang-Menghai seismic belt has not been fully studied yet.In the present work,we conducted tectonic geomorphic indices to analyze the relative tectonic activity along the faults in the seismic belt based on the digital elevation model.We interpreted asymmetric factor,index of drainage basin shape,hypsometric integral,normalized streamlength gradient,valley floor-to-width to height ratio,and longitudinal profiles to show that the relative tectonic activity is higher in the north and lower in the south,and is strong in the region from Shanjia to Huimin in the center of the seismic belt.

Erratum to: Evaluation of the Relative Tectonic Activity from the Faults in the Gengma-Lancang-Menghai Seismic Belt (Southwestern China)

The original version of this article unfortunately contained a mistake.The presentation of an author's name was incorrect.The corrected oneis given below.

Isorhamnetin protects zearalenone-induced damage via the PI3K/Akt signaling pathway in porcine ovarian granulosa cells

Zearalenone(ZEA)is widely derived from moldy cereal grain,which has adverse effects on animal reproduction.In particular,pigs are more sensitive to ZEA-induced toxicity than other animals.Isorhamnetin has extensive pharmacological activity.However,the role of isorhamnetin in ZEA-induced cytotoxicity remains unclear.This study was designed to investigate the therapeutic effect of isorhamnetin on ZEA-induced damage in porcine ovarian granulosa cells and elucidate its molecular mechanism.Two experiments were conducted,where a minimum of 3 biological replicates were used for each treatment.In Exp.1,ovarian granulosa cells were treated with different concentrations of isorhamnetin(1,5,10,20 and 30μmol/L)and ZEA(0,10,30,60,90 and 120μmol/L)for 24 h.Our results indicated that 60μmol/L ZEA(half-maximal inhibitory concentration value)and 20μmol/L isorhamnetin(the most effective concentration against ZEA-induced cytotoxicity)were optimum concentrations.In Exp.2,ovarian granulosa cells were treated with isorhamnetin(20μmol/L)for 2 h,before treatment with ZEA(60μmol/L)for 24 h.Apoptosis,endoplasmic reticulum stress,oxidative stress,proliferation and hormone secretion of ovarian granulosa cells were detected.Our findings showed that isorhamnetin suppressed(P<0.05)ZEA-induced apoptosis by altering mitochondrial membrane potential and apoptosis-related proteins(B-cell lymphoma-2[Bcl-2],Bcl2-associated x[Bax]and cleaved caspase-3[C-Casp3]).Changes in intracellular Ca2+levels and C/EBP homologous protein(CHOP),recombinant activating transcription factor 6(ATF6),glucose regulated protein78 k D(GRP78)indicated that isorhamnetin rescued(P<0.05)ZEA-induced endoplasmic reticulum stress.Furthermore,isorhamnetin prevented(P<0.05)ZEA-induced oxidative stress via the mitogen-activated protein kinase(P38)signaling pathway.Mechanistically,isorhamnetin stimulated(P<0.05)the expression of proliferating cell nuclear antigen(PCNA)and cyclin D,thereby increasing the ratio of S phase cells in response to ZEAinduced apoptosis via phosphatidylinositol 3 kinase/protein kinase B(PI3K/Akt)signaling pathway.Isorhamnetin also recovered(P<0.05)ZEA-induced steroidogenesis disorder by regulating steroidogenic enzyme gene and proteins(follicle-stimulating hormone receptor[FSHR]and cytochrome P450 family 19subfamily a member 1[CYP19A1]).Collectively,these findings show that isorhamnetin protects ovarian granulosa cells from ZEA-induced damage,which promotes proliferation,alleviates apoptosis,endoplasmic reticulum stress,oxidative stress,and steroidogenesis disorder.

Cenozoic Uplift of the Central Yunnan Fragment, Southwestern China, Revealed by Apatite(U-Th)/He Dating

The age of central Yunnan fragment uplift has long been debated, with estimates ranging from the Late Eocene to about 1 Ma. To determine the central Yunnan fragment uplift time in the Cenozoic, apatite(U-Th)/He(AHe) was used to analyze the low-temperature thermochronology of samples from the Jiaozi Mountain area of the eastern central Yunnan fragment. The sampling area is located in the Dongchuan District of Kunming, Yunnan Province, near the Xiaojiang fault zone. The results show that AHe ages from the eastern part of central Yunnan fragment were mainly concentrated around 25.7–37.9 Ma, and intensive uplift had happened before 36.5 Ma. Together with previous low-temperature thermochronology research on the western and eastern central Yunnan fragment, we concluded that the Yunnan Plateau uplifted prior to 36.5 Ma, in a west to east sequence. The uplift caused a change in paleo-geographical terrain, which may have altered the ancient river systems of the southeast Tibetan Plateau.